Question

Prologue: Alice Kaninchenbau was a 20-year-old junior at Boise St. University, where she majored in Political Science and played as an open-side flanker on the women’s rugby team. In the last game of the season (against Weber St.) she suffered a broken nose (and the team suffered a 0-36 loss). Always an optimist, Alice considered her broken nose to be the perfect reason to have a rhinoplasty (and get the nose she had always wanted). The case: The antibiotic erythromycin was administered 24 hour before the surgery, and the procedure was uneventful. Twelve hours post-operatively, however; she experienced sudden nausea. Alice called for the nurse. As the nurse arrived, Alice vomited. While the nurse helped her to the bathroom Alice experienced dizziness, and complained of muscle aches in her legs and shoulders, and then experienced syncope. The nurse got her back to the bed, elevated her legs, and called for a physician from the ER. When the ER physician arrived two minutes later, Alice was conscious but listless. On examination, her temperature was 40.2˚C, with elevated heart and respiration rates (165 beats per minute and 26 breaths per minute). Her blood pressure was depressed (88/50). One liter of physiological saline was administered intravenously, and her blood pressure was briefly restored to 110/70. Physical examination revealed marked hyperemia of the conjunctivae and oral mucosa, bilateral nasal packing (to control postsurgical bleeding), supple neck, diffuse pulmonary rales, edema of the hands and feet, a red rash on her trunk and extremities with petechiae evident, but no generalized lymphadenopathy or hepatosplenomegaly, nor any signs of local infection. At this point she was moved into intensive care, with intravenous nafcillin begun. Her blood pressure fell to 90/40, at which time she received 500 ml of 5% albumin intravenously and was intubated, with 100% oxygen provided. Pulmonary edema fluid bubbled freely from the intubation tube. A dopamine drip was used to increase cardiac output and additional fluids were given to maintain a systolic pressure of 90. An electrocardiogram was performed and showed relatively normal heart function. Extensive laboratory tests were performed. Her white blood cell count was elevated (20,500 cells µl-1 ), with a predominance of neutrophils and band forms (immature neutrophils – indicating rapid mobilization of new neutrophils from the bone marrow). Serum electrolyte levels were in the normal range, SGOT and alkaline phosphatase levels were at the high end of normal, however, her CPK levels were elevated at 1,600 U L-1 . Her urine was positive for blood, glucose, and ketones. Blood coagulation time was prolonged; but the hematocrit (40%) and platelet count (245,400 cells µl-1 ) were normal. Cerebrospinal fluid (CSF) was normal, and upon microscopic examination showed no evidence of infection. Cultures of blood, urine, CSF, and vaginal fluid (she was not menstruating) were made. The nasal packing was removed from her nose and found to contain pus. The pus was Gram-stained, revealing the presence of PMNs in sheets, with both intracellular and extracellular Gram-positive cocci in clusters. She was immediately given intravenous oxacillin, clindamycin, and cefotaxime, along with intravenous immunoglobulin (IVIG). CS05 Due 10/18/19 For the next twelve-hours she was continually transfused with over eight liters of albumin, fresh frozen plasma and saline to stabilize and maintain her blood pressure. Her urinary output was robust, and she slowly improved. She was extubated and provided 30% oxygen by facial mask. Twelve hours later she was transferred to the regular in-patient ward. Her blood, urine, CSF and vaginal fluid cultures were negative for pathogenic bacteria, however; the pus from her nasal packing was positive for Staphylococcus aureus. Her antibiotic treatment was continued for seven days, which were uneventful, except for the slow fading of her rash. After a total of nine days in the hospital she was released. Epilogue: The S. aureus strain recovered from Alice’s nasal packing was subsequently sent to the Centers for Disease Control, where it was determined that this strain carried the tsst-1 gene. Note that the TSST-1 protein has been classified as a “super-antigen”.

Questions:

1.) From the epilogue, it is straightforward to determine the disease Alice had.

a.) What is the disease?

b.) Explain why her blood pressure dropped, and why she developed pulmonary edema.

c.) Her CPK levels were elevated – this can mean a number of things – but what is it indicative of in this case?

2.) Explain how TSST-1 can cause the symptoms Alice experienced.

3.) This disease primarily occurs in people with the specific HLA haplotypes DR7DQ2, DR14DQ5, DR4DQ8, and DR8DQ4. Explain why people with these haplotypes are more likely to have this disease than those that have different haplotypes.

4.) If you took the T-cells from Alice’s blood, reacted them with fluorescently-labelled antibodies specific for the variable region of the b-chain of the T-cell receptor, and examined them by flow cytometry*, you would find that over ½ of all her T-cells were expressing T-cell receptors with the Vb2 version of the variable region. This seems strange, given that there are 48 different Vb segments that a b-chain can be made from. Strange, but real – what does this observation tell you about this disease?

5.) Having experienced this disease once, would you expect Alice to now be immune? Explain why, or why not.

Answer 1

1) The nasal packing was removed from her nose and found to contain pus. The pus was Gram-stained, revealing the presence of PMNs in sheets, with both intracellular and extracellular Gram-positive cocci in clusters.The cardinal signs and symptoms of Ms Alice shows that she suffered with "Toxic Shock Syndrome" . TST is defined as lethal infection caused by Group A streptococcus , a gram positive bacteria.

2) Superantigens are exotoxins normally acts on T cells ( lymphocyte cells). Exotoxins aggravates T cells resulting in excessive production of cytokine release. This results in enormous tissue injury and end up with Multi organ failure. Cytokines are inflammatory mediators results in vasodilation, and it decreases systemic vascular resistance resulting in hypotension.

Pulmonary edema is a lethal complication occurs due to streptococcal toxic syndrome. After aggravation of cytokines mediators nitric oxide is released from damaged tissues resulting in vasodilation. These inflammatory mediators triggers alveolar damage and hyaline membrane damage resulting in excess fluid collection in alveoli.

3) CPK is creatine phosphokinase is an enzyme normally found in brain,heart and skeletal muscles. Any injury to theses muscles results in elevated CPK. Toxic shock syndrome results in massive damage to the tissues of vital organs resulting in elevated CPK.

4) The symptoms of hypotension results from triggering of T lymphocytes by exotoxins that further contributes to aggravation of cytokines release and end up with decrease systemic vascular resistance. Edema results from cardiogenic shock secondary to exotoxins affecting heart muscles.

5) Human leukocyte antigen helps brain to identify the difference between normal body cells or a pathogen. When human is exposed to any infectious agents like virus, bacteria or fungi the HLA identify pathogens and initiates phagocytosis. HLA are inherited from parents to offsprings. HLA antigens triggers certain autoimmune diseases like SLE,Myasthenia gravis.